The impact of a Western diet and binge drinking on metabolic dysfunction-associated steatotic liver disease in male and female mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern, largely driven by the high-fat, high-sugar and low-fibre Western diet. The Western diet is often accompanied by binge drinking, or the rapid consumption of alcohol in a short time leading to a blood alcohol concentration of ≥0.08%. Emerging evidence suggests that co-consumption of a Western diet and binge drinking might converge on shared pathological mechanisms in males, but little is known about the role of sex in this interaction. Given these complex interactions between diet, alcohol, sex and liver health, we sought to investigate how the addition of binge drinking to a Western diet impacts MASLD progression in male and female mice. Young (6-week-old) male and female C57BL6/J mice (n = 9-11 per sex per group) were assigned to the following groups: Control, Control/Binge, Western, or Western/Binge. Following 12 weeks of treatment, Western diet, regardless of binge drinking, resulted in increased hepatic lipid accumulation and oxidative damage in both sexes, with males showing more evidence of disease than females. In general, male mice in the Western binge group had the most pronounced evidence of liver damage among males, whereas female mice in the Western diet group tended to have more evidence of disease than all other female groups as measured by histology, serum transaminases and immunohistochemistry. The collective results suggest that addition of binge drinking to a Western diet can result in a more progressive form of liver disease in males and that sex plays a key role in response to the combination of unhealthy diet and binge drinking.